About TSC2
No gene-level summary was recorded for this case.
Previous versions
Variant interpretation report
TSC2 c.729C>G, p.(Leu243=)
Classification
Benign
Variant description:
No variant summary was recorded for this case.
Five-step scale from benign to pathogenic. This variant is benign. Select a step to read what it means.
Benign.A benign classification under the recorded framework.
In plain language
Gene-level background from the recorded interpretation.
Words with a dotted underline have a short definition. Hover or tap them.
LYFE Sciences is an AI system, and it can make mistakes.
Criteria may be applied incorrectly, sources may be misread, and a
confident-looking classification can still be wrong.
Double-check every criterion and its underlying evidence
before relying on any call.
01The reasoning
How it was classified
The recorded framework is Not recorded. The criteria and strengths shown below come from the saved assessment; this page does not recalculate the classification.
Recorded applied criteria
The applied criteria and their strengths are shown as assessed under the stated framework.
Pathogenic evidence criteria: 0
Benign evidence criteria: 5
Pathogenic criteria applied · 0
No pathogenic criterion marked as applied in the recorded assessment.
Benign criteria applied · 5
BS1Strong
BS1 · strong
The allele frequency of NM_000548.5:c.729C>G exceeds the BS1 threshold of >0.3% in the general population. gnomAD v2.1: 0.355% (1000/281,464 alleles, 0 homozygotes), gnomAD v4.1: 0.316% (5,099/1,612,278 alleles, 10 homozygotes). This frequency is substantially greater than expected for TSC2-associated tuberous sclerosis complex (incidence ~1:6,000-10,000).
BS2Strong
BS2 · strong
NM_000548.5:c.729C>G has been observed in 10 homozygous individuals in gnomAD v4.1 (total AF=0.316%, 5,099 heterozygous alleles). Tuberous sclerosis complex is a dominant disorder with high penetrance. Observation of homozygotes and thousands of heterozygotes in a population database of generally healthy individuals constitutes strong evidence for a benign role.
BP4Supporting
BP4 · supporting
Multiple lines of computational evidence suggest no impact on gene product. SpliceAI predicts no significant splice alteration (max delta score = 0.01). NM_000548.5:c.729C>G is a synonymous variant (p.Leu243=) at a nucleotide position where in silico splicing predictions support a null effect.
BP6Supporting
BP6 · supporting
Multiple reputable clinical laboratories consistently classify NM_000548.5:c.729C>G as Benign or Likely benign in ClinVar (Variation ID 49382). Fifteen clinical laboratories classify as Benign and six as Likely benign, with criteria provided. No submitting laboratory has asserted pathogenicity.
BP7Supporting
BP7 · supporting
NM_000548.5:c.729C>G is a synonymous variant (p.Leu243=) for which splicing prediction algorithms predict no impact on splicing. SpliceAI max delta score is 0.01, well below the 0.10 threshold for predicted splice alteration. The nucleotide is not evolutionarily constrained to a degree suggesting functional importance.
Recorded classification: Benign
gene-specific framework lacked a usable explicit final combination framework, so generic ACMG/AMP 2015 final-combination rules were applied as fallback; applied criteria: BS1 strong benign, BS2 strong benign, BP4 supporting benign, BP6 supporting benign, BP7 supporting benign; combination = 2 strong benign + 3 supporting benign, which maps to Benign.
02The sources
Evidence at a glance
Evidence summaries and captured source records, where available. Missing entries should not be interpreted as negative findings.
gnomAD v4.1
gnomAD v2.1
Population frequency
5,099 / 1,612,278 alleles
gnomAD v4.1: 5,099 / 1,612,278 alleles. Recorded AF 0.00316261. Recorded homozygote count 10.
gnomAD v2.1
This variant is present in gnomAD v2.1 (AF= 0.00355285; MAF= 0.35529%, 1000/281464 alleles, homozygotes = 0) and has highest observed frequency in the European (Finnish) population (AF= 0.0119589; MAF= 1.19589%, 284/23748 alleles, homozygotes = 0); grpmax FAF= 0.0056912.
SpliceAI score
0.010 maximum delta
Recorded SpliceAI maximum delta score: 0.010. Refer to the recorded PP3/BP4 rationale for interpretation.
ClinVar submissions
21 reported laboratory submissions
15 Benign · 6 Likely benign.
Functional evidence
Statement recorded
OncoKB identified curated literature and non-variant-specific oncogenicity context for review; listed oncogenicity label: Unknown Oncogenic Effect.
No listed criterion applied
OncoKB ↗
COSMIC
Cancer Hotspots
Somatic evidence
2 recorded samples
This variant has previously been reported in somatic cancers (COSMIC; COSV104587071, n = 2 times).
Cancer Hotspots
This variant does not lie in a statistically significant hotspot.
Context only
For specialists
Technical detail
ACMG/AMP criteria under Not recorded, with the data and sources behind each one.
26 criteria with recorded statuses: 5 met · 11 not met · 5 not assessed · 5 not applicable. Open any row for the full reasoning, the rule and the evidence behind it.
Met
Not met
Not assessed
Not applicable
NM_000548.5:c.729C>G (p.Leu243=) is a synonymous variant in exon 8 of TSC2 with an overall allele frequency of 0.316-0.355% in gnomAD, exceeding the BS1 threshold of >0.3%.
This variant has been observed in 10 homozygous individuals in gnomAD v4.1 among 1,612,278 alleles, constituting strong evidence for benignity in a dominant disorder (BS2).
SpliceAI predicts no splice impact (max delta = 0.01), and the variant is synonymous with no predicted effect on protein sequence, supporting multiple benign computational evidence lines (BP4, BP7).
ClinVar classifies this variant as Benign/Likely benign across 21 clinical laboratory submissions (15 Benign, 6 Likely benign), with criteria provided and no conflicting pathogenic interpretations (BP6).
No pathogenic criteria are met. PVS1, PS1, and PM5 are not applicable to this synonymous variant. PS2, PS3, PS4, PS5, PM1, PM2, PM6, PP3, and PP5 are not met. PP1, PP4, BS4, BP2, and BP5 are not assessed due to absence of data. BA1 is not met (overall AF <1%). BP1 and PP2 are not applicable to synonymous variants.
Applying generic ACMG/AMP 2015 final combination rules: two strong benign criteria (BS1, BS2) alone satisfy the classification threshold for Benign. Additionally, three supporting benign criteria (BP4, BP6, BP7) reinforce the benign classification.
No criteria match.
Met · 5
BS1 StrongThe allele frequency of NM_000548.5:c.729C>G exceeds the BS1 threshold of >0.3% in the general population. gnomAD v2.1: 0.355% (1000/281,464 alleles, 0 homozygotes), gnomAD v4.1: 0.316% (5,099/1,612,278 alleles, 10 homozygotes). This frequency is substantially greater than expected for TSC2-associated tuberous sclerosis complex (incidence ~1:6,000-10,000). Details ▾Hide ▴
Evidence considered
- gnomAD v2.1: AF=0.355% (>0.3% BS1 threshold)
- 1000/281464 alleles
- v4.1: AF=0.316%
- 5099/1612278 alleles
- 10 homozygotes.
Sources
BS2 StrongNM_000548.5:c.729C>G has been observed in 10 homozygous individuals in gnomAD v4.1 (total AF=0.316%, 5,099 heterozygous alleles). Tuberous sclerosis complex is a dominant disorder with high penetrance. Observation of homozygotes and thousands of heterozygotes in a population database of generally healthy individuals constitutes strong evidence for a benign role. Details ▾Hide ▴
Evidence considered
- gnomAD v4.1: 10 homozygotes observed
- 5
- 099 total alternate alleles. Dominant disorder observation in healthy population.
Sources
BP4 SupportingMultiple lines of computational evidence suggest no impact on gene product. SpliceAI predicts no significant splice alteration (max delta score = 0.01). NM_000548.5:c.729C>G is a synonymous variant (p.Leu243=) at a nucleotide position where in silico splicing predictions support a null effect. Details ▾Hide ▴
Evidence considered
- SpliceAI max delta = 0.01 (no predicted splice impact)
- synonymous substitution with no predicted effect on protein sequence or splicing.
Sources
BP6 SupportingMultiple reputable clinical laboratories consistently classify NM_000548.5:c.729C>G as Benign or Likely benign in ClinVar (Variation ID 49382). Fifteen clinical laboratories classify as Benign and six as Likely benign, with criteria provided. No submitting laboratory has asserted pathogenicity. Details ▾Hide ▴
Evidence considered
- ClinVar Variation ID 49382: Benign by 15 clinical labs
- Likely benign by 6 clinical labs
- multiple submitters with criteria provided
- no expert panel disagreement.
Sources
BP7 SupportingNM_000548.5:c.729C>G is a synonymous variant (p.Leu243=) for which splicing prediction algorithms predict no impact on splicing. SpliceAI max delta score is 0.01, well below the 0.10 threshold for predicted splice alteration. The nucleotide is not evolutionarily constrained to a degree suggesting functional importance. Details ▾Hide ▴
Evidence considered
- Synonymous variant p.(Leu243=)
- SpliceAI max delta = 0.01 (no predicted splice impact)
- nucleotide position not at a conserved splice-relevant site.
Sources
Not met · 11 · evaluated, threshold not reached
PS2 No de novo occurrence with confirmed maternity and paternity has been reported for NM_000548.5:c.729C>G. PMID:15798777 (Sancak et al. 2005) reported TSC1/TSC2 mutations in 490 TSC patients and noted de novo TSC2 mutations, but the specific variant c.729C>G was not identified in the abstract and full-text confirmation is unavailable. Details ▾Hide ▴
Evidence considered
- No de novo observation with confirmed parentage identified for this variant.
Still missing
- Full-text of PMID:15798777 was not available to confirm whether c.729C>G was observed among de novo cases.
Sources
15798777
PS3 No well-established in vitro or in vivo functional studies have been identified that demonstrate a damaging effect of NM_000548.5:c.729C>G on TSC2 function or splicing. PMID:24033266 and PMID:25741868 are methodological and guideline papers, not functional studies of this variant. Details ▾Hide ▴
Evidence considered
- No functional study data available for c.729C>G.
Still missing
- No functional data specific to this variant.
Sources
2403326625741868
PS4 No case-control studies demonstrating statistically significant enrichment of NM_000548.5:c.729C>G in affected individuals compared to controls have been identified. PMID:15798777 studied TSC patients but the abstract does not mention this variant. The variant is present at appreciable frequency (0.3-0.4%) in population databases, making it unlikely to be enriched in disease cohorts. Details ▾Hide ▴
Evidence considered
- Population frequency (gnomAD v2.1: 0.355%
- v4.1: 0.316%) is inconsistent with a rare pathogenic variant for TSC (incidence ~1:6
- 000-10
- 000).
Sources
PM1 NM_000548.5:c.729C>G is not located in a recognized mutational hotspot or well-established critical functional domain of TSC2 without benign variation. The residue Leu243 is not in a statistically significant hotspot (cancerhotspots.org). Details ▾Hide ▴
Evidence considered
- Residue Leu243 is not in a statistically significant hotspot
- no TSC2-specific PM1 domain has been defined for generic ACMG assessment.
Still missing
- No CSPEC/VCEP-defined TSC2 critical domains exist for PM1 adjudication.
PM2 NM_000548.5:c.729C>G is present in gnomAD at allele frequencies well above the 0.1% PM2 threshold. gnomAD v2.1: 0.355% (1000/281464 alleles), gnomAD v4.1: 0.316% (5099/1,612,278 alleles). This variant is too common in population databases to qualify as absent/rare under PM2. Details ▾Hide ▴
Evidence considered
- gnomAD v2.1 AF=0.355% (>0.1%)
- v4.1 AF=0.316% (>0.1%).
Sources
PM6 No de novo occurrence of NM_000548.5:c.729C>G has been reported without confirmation of paternity/maternity. PMID:15798777 analyzed TSC1/TSC2 mutations including de novo cases, but the specific variant c.729C>G was not identified in the abstract and full-text is unavailable for confirmation. Details ▾Hide ▴
Evidence considered
- No de novo observation (without parentage confirmation) identified for this variant.
Still missing
- Full-text of PMID:15798777 was not available to confirm variant presence.
Sources
15798777
PP3 Multiple lines of computational evidence do not support a deleterious effect. SpliceAI predicts no significant splice impact (max delta score = 0.01). REVEL and BayesDel scores are unavailable for this variant. The synonymous nature of the variant (p.Leu243=) is itself computationally predicted to be silent. Details ▾Hide ▴
Evidence considered
- SpliceAI max delta = 0.01 (no predicted splice impact)
- synonymous substitution at a residue without computational evidence of pathogenicity.
Still missing
- REVEL and BayesDel scores unavailable for this genomic position.
Sources
PP5 PP5 requires a reputable source to report the variant as pathogenic. ClinVar classifies NM_000548.5:c.729C>G as Benign (15 clinical laboratories) and Likely benign (6 clinical laboratories). No reputable source has asserted pathogenicity for this variant. Details ▾Hide ▴
Evidence considered
- ClinVar Variation ID 49382: classified as Benign by 15 labs
- Likely benign by 6 labs
- no pathogenic assertions.
Sources
BA1 The overall allele frequency of NM_000548.5:c.729C>G in gnomAD is below the BA1 threshold of >1%. gnomAD v2.1 overall AF=0.355%, v4.1 overall AF=0.316%. While the Finnish subpopulation frequency exceeds 1% (v2.1: 1.20%, v4.1: 1.21%), BA1 is assessed on overall population frequency per standard ACMG/AMP interpretation. Details ▾Hide ▴
Evidence considered
- Overall gnomAD AF: v2.1=0.355%
- v4.1=0.316%
- both below 1% BA1 threshold.
Sources
BS3 No well-established in vitro or in vivo functional studies demonstrating no deleterious effect of NM_000548.5:c.729C>G have been identified. PMID:24033266 and PMID:25741868 are methodological/guideline papers and do not contain functional data for this variant. Details ▾Hide ▴
Evidence considered
- No functional studies demonstrating a benign effect for this specific variant.
Still missing
- No functional data for c.729C>G.
Sources
2403326625741868
PS5 PS5 applies when a reputable source reports the variant as pathogenic but independent evidence is unavailable. ClinVar classifies this variant as Benign (15 clinical laboratories) and Likely benign (6 clinical laboratories). No reputable source has asserted pathogenicity. Details ▾Hide ▴
Evidence considered
- ClinVar Variation ID 49382: Benign (15 labs)
- Likely benign (6 labs). No pathogenic assertions from reputable sources.
Sources
Not assessed · 5 · no assessment recorded
PP1 No cosegregation data are available for NM_000548.5:c.729C>G. No family studies with this variant have been identified in the reviewed literature. Details ▾Hide ▴
Evidence considered
- No cosegregation information available.
Still missing
- Cosegregation data would require family studies with this variant
- none identified.
PP4 No specific patient phenotype data are available for independent review. The variant is classified as Benign/Likely benign by multiple clinical laboratories in ClinVar, suggesting it is observed in individuals without TSC-specific phenotypes, but individual-level phenotype data are not accessible. Details ▾Hide ▴
Evidence considered
- ClinVar submissions indicate the variant is observed in clinical testing contexts
- but individual phenotype details are not available.
Still missing
- Individual patient phenotype data not available for review.
Sources
BS4 No cosegregation data in affected families are available for NM_000548.5:c.729C>G. Lack of segregation with disease cannot be assessed without family studies. Details ▾Hide ▴
Evidence considered
- No segregation data available.
Still missing
- Family cosegregation data needed for BS4 assessment.
BP2 No data are available regarding observation of NM_000548.5:c.729C>G in trans with a known pathogenic TSC2 variant. While the presence of 10 homozygotes in gnomAD v4.1 effectively demonstrates observation in trans (biallelic), formal assessment would require individual-level genotype data. Details ▾Hide ▴
Evidence considered
- 10 homozygotes in gnomAD v4.1 suggest biallelic observation
- but individual-level phasing data are not available.
Still missing
- Individual-level genotype data to confirm trans configuration with known pathogenic variants.
Sources
BP5 No case has been identified where NM_000548.5:c.729C>G was found in an individual with an alternate molecular basis for disease. This information is typically available only from detailed clinical reports. Details ▾Hide ▴
Evidence considered
- No data on alternate molecular basis in cases carrying this variant.
Still missing
- Clinical case-level data with alternate molecular diagnoses not available.
Not applicable · 5· recorded as not applicable Show reasons ▾Hide reasons ▴
PVS1 N/ANM_000548.5:c.729C>G is a synonymous variant (NP_000539.2:p.(Leu243=)) and does not fall into any PVS1 null-variant category (nonsense, frameshift, or canonical ±1,2 splice consensus). Per ClinGen SVI PVS1 framework (PMC6185798), the generic PVS1 decision algorithm is not applied to synonymous variants. Details ▾Hide ▴
Evidence considered
- Synonymous variant p.(Leu243=) produces no premature termination codon or splice consensus disruption.
Sources
pvs1_generic_framework ↗pvs1_variant_assessment
PS1 N/APS1 applies when the same amino acid change has been established as pathogenic via a different nucleotide change. NM_000548.5:c.729C>G is a synonymous variant (p.Leu243=) that does not alter the amino acid sequence, so there is no amino acid change to compare against known pathogenic variants. Details ▾Hide ▴
Evidence considered
- Synonymous variant produces no amino acid change
- criterion not applicable.
PM5 N/APM5 requires a different missense change at the same residue that has been established as pathogenic. NM_000548.5:c.729C>G is a synonymous variant (p.Leu243=) with no amino acid change; there is no altered residue to compare against known pathogenic missense variants at position 243. Details ▾Hide ▴
Evidence considered
- Synonymous variant (p.Leu243=)
- no amino acid substitution to evaluate under PM5.
Sources
pm5_candidates
PP2 N/APP2 is specific to missense variants in genes where missense variants are a common disease mechanism and benign missense variation is low. NM_000548.5:c.729C>G is a synonymous variant (p.Leu243=), not a missense change. Details ▾Hide ▴
Evidence considered
- Synonymous variant
- PP2 applies only to missense variants.
BP1 N/ABP1 applies to missense variants in genes where truncating variants are the primary mechanism of disease. NM_000548.5:c.729C>G is a synonymous variant (p.Leu243=), not a missense change. Additionally, TSC2 disease is caused by both missense and truncating variants. Details ▾Hide ▴
Evidence considered
- Synonymous variant
- BP1 applies only to missense variants.
Identifiers
- Gene
- TSC2
- Transcript
- NM_000548.5
- Coding (HGVS c.)
- NM_000548.5:c.729C>G
- Protein (HGVS p.)
- NP_000539.2:p.(Leu243=)
- GRCh38
- chr16:2056724 C>G
- GRCh37
- chr16:2106725 C>G
- ClinVar
- 49382
- COSMIC
- COSV104587071
Gene diagram
Every interpreted variant in TSC2, mapped onto the exon structure of NM_000548.5. Select a row to find it on the plot.
TSC2NM_000548.5
Fetching transcript structure from UCSC…
Exons
—
Transcript span
—
Strand
—
Variants mapped
—
Source
UCSC ncbiRefSeqCurated
All variants in TSC2
—
Select a row to find it on the plot; use the link to open its page.
| Protein | Location | Classification | Link |
|---|
gnomAD v4.1
5,099 / 1,612,278 alleles
AF 0.00316 · 10 homozygotes · FAF 0.00305
gnomAD v2.1
1,000 / 281,464 alleles
AF 0.00355 · 0 homozygotes · FAF 0.00569
gnomAD-Canada v1.0
0 / 0 alleles
AF 0 · 0 homozygotes · FAF 0
By genetic ancestry
gnomAD v4.1
AF 0.0032 · 5099 / 1,612,278 alleles · 10 hom · FAF 0.003
| European (Finnish)753 / 62,138 | 0.0124 hom |
| Ashkenazi Jewish119 / 29,606 | 0.004 |
| European (non-Finnish)3696 / 1,180,020 | 0.00315 hom |
| Remaining individuals193 / 62,492 | 0.0031 |
| South Asian210 / 91,084 | 0.0023 |
| Admixed American94 / 60,024 | 0.00161 hom |
| Middle Eastern3 / 6,062 | 0.00049 |
| African/African American31 / 75,050 | 0.00041 |
0 alternate alleles recorded in 2 other groups: Amish, East Asian.
gnomAD v2.1
AF 0.0036 · 1000 / 281,464 alleles · 0 hom · FAF 0.0057
| European (Finnish)284 / 23,748 | 0.012 |
| Ashkenazi Jewish47 / 10,370 | 0.0045 |
| Remaining individuals30 / 7,218 | 0.0042 |
| European (non-Finnish)507 / 129,170 | 0.0039 |
| South Asian57 / 30,616 | 0.0019 |
| Admixed American59 / 35,438 | 0.0017 |
| African/African American16 / 24,956 | 0.00064 |
0 alternate alleles recorded in 1 other group: East Asian.
gnomAD-Canada
AF 0 · 0 / 0 alleles · 0 hom
Statements
gnomAD v4.1
This variant is present in gnomAD v4.1 (AF= 0.00316261; MAF= 0.31626%, 5099/1612278 alleles, homozygotes = 10) and has highest observed frequency in the European (Finnish) population (AF= 0.0121182; MAF= 1.21182%, 753/62138 alleles, homozygotes = 4); grpmax FAF= 0.00304706.
gnomAD v2.1
This variant is present in gnomAD v2.1 (AF= 0.00355285; MAF= 0.35529%, 1000/281464 alleles, homozygotes = 0) and has highest observed frequency in the European (Finnish) population (AF= 0.0119589; MAF= 1.19589%, 284/23748 alleles, homozygotes = 0); grpmax FAF= 0.0056912.
SpliceAI and Pangolin
Other predictors
- REVEL
- Not available
- BayesDel
- Not available
How the predictions were used
BP4 SupportingMultiple lines of computational evidence suggest no impact on gene product. SpliceAI predicts no significant splice alteration (max delta score = 0.01). NM_000548.5:c.729C>G is a synonymous variant (p.Leu243=) at a nucleotide position where in silico splicing predictions support a null effect. Details ▾Hide ▴
Evidence considered
- SpliceAI max delta = 0.01 (no predicted splice impact)
- synonymous substitution with no predicted effect on protein sequence or splicing.
Sources
BP7 SupportingNM_000548.5:c.729C>G is a synonymous variant (p.Leu243=) for which splicing prediction algorithms predict no impact on splicing. SpliceAI max delta score is 0.01, well below the 0.10 threshold for predicted splice alteration. The nucleotide is not evolutionarily constrained to a degree suggesting functional importance. Details ▾Hide ▴
Evidence considered
- Synonymous variant p.(Leu243=)
- SpliceAI max delta = 0.01 (no predicted splice impact)
- nucleotide position not at a conserved splice-relevant site.
Sources
PP3 Multiple lines of computational evidence do not support a deleterious effect. SpliceAI predicts no significant splice impact (max delta score = 0.01). REVEL and BayesDel scores are unavailable for this variant. The synonymous nature of the variant (p.Leu243=) is itself computationally predicted to be silent. Details ▾Hide ▴
Evidence considered
- SpliceAI max delta = 0.01 (no predicted splice impact)
- synonymous substitution at a residue without computational evidence of pathogenicity.
Still missing
- REVEL and BayesDel scores unavailable for this genomic position.
Sources
Statement
In silico
SpliceAI predicts no significant splice impact for this variant (max delta score = 0.01).
9 paper records listed. No publication is explicitly linked to an applied criterion in the recorded metadata. None of the listed paper records explicitly indicates that the variant is named.
Recorded publications
-
PMID 15798777 ↗Mutational analysis of the TSC1 and TSC2 genes in a diagnostic setting: genotype--phenotype correlations and comparison of diagnostic DNA techniques in Tuberous Sclerosis Complex.Sancak O et al. · 2005No paper-specific finding is recorded.
-
PMID 24033266 ↗A systematic approach to assessing the clinical significance of genetic variants.No paper-specific finding is recorded.
-
PMID 25741868 ↗Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.Richards S et al. · 2015No paper-specific finding is recorded.
-
PMID 9829910 ↗Exon scanning of the entire TSC2 gene for germline mutations in 40 unrelated patients with tuberous sclerosis.No paper-specific finding is recorded.
-
PMID 20301399 ↗Tuberous Sclerosis Complex.Adam MP et al. · 1993No paper-specific finding is recorded.
-
PMID 23519317 ↗Clinical genetics evaluation in identifying the etiology of autism spectrum disorders: 2013 guideline revisions.Schaefer GB et al. · 2013No paper-specific finding is recorded.
-
PMID 23788249 ↗ACMG recommendations for reporting of incidental findings in clinical exome and genome sequencing.Green RC et al. · 2013No paper-specific finding is recorded.
-
PMID 25356965 ↗ACMG policy statement: updated recommendations regarding analysis and reporting of secondary findings in clinical genome-scale sequencing.ACMG Board of Directors · 2015No paper-specific finding is recorded.
-
PMID 28492532 ↗Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.No paper-specific finding is recorded.
Screenshots represent source records captured during evidence collection. Select one to view the recorded source content.
gnomAD v4.1
5,099 / 1,612,278 recorded alleles
Open source ↗
gnomAD v2.1
Captured gnomAD v2.1 source record
Open source ↗
SpliceAI Lookup
Recorded maximum delta 0.010
Open source ↗
ClinVar
15 Benign · 6 Likely benign
Open source ↗
COSMIC
Captured COSMIC source record
Open source ↗
Cancer hotspots
Captured Cancer Hotspots source record
Open source ↗
OncoKB
Captured OncoKB source record
Open source ↗
All source links
- ClinVar ↗www.ncbi.nlm.nih.gov/clinvar/variation/49382/
- gnomAD v2.1 ↗gnomad.broadinstitute.org/variant/16-2106725-C-G?dataset=gnomad_r2_1
- gnomAD v4.1 ↗gnomad.broadinstitute.org/variant/chr16-2056724-C-G?dataset=gnomad_r4
- SpliceAI Lookup ↗spliceailookup.broadinstitute.org/#variant=NM_000548.5%3Ac.729C…
- OncoKB ↗www.oncokb.org/gene/TSC2/L243=
- COSMIC ↗cancer.sanger.ac.uk/cosmic/mutation/overview?id=120473369
- Cancer hotspots ↗www.cancerhotspots.org/
Statements for reports
The evidence statements recorded by the interpretation pipeline. They have not been reinterpreted by the page.
gnomAD v4.1
This variant is present in gnomAD v4.1 (AF= 0.00316261; MAF= 0.31626%, 5099/1612278 alleles, homozygotes = 10) and has highest observed frequency in the European (Finnish) population (AF= 0.0121182; MAF= 1.21182%, 753/62138 alleles, homozygotes = 4); grpmax FAF= 0.00304706.
gnomAD v2.1
This variant is present in gnomAD v2.1 (AF= 0.00355285; MAF= 0.35529%, 1000/281464 alleles, homozygotes = 0) and has highest observed frequency in the European (Finnish) population (AF= 0.0119589; MAF= 1.19589%, 284/23748 alleles, homozygotes = 0); grpmax FAF= 0.0056912.
ClinVar
This variant has been reported in ClinVar as Benign (15 clinical laboratories) and as Likely benign (6 clinical laboratories). (ClinVarID = 49382)
In silico
SpliceAI predicts no significant splice impact for this variant (max delta score = 0.01).
Functional
OncoKB identified curated literature and non-variant-specific oncogenicity context for review; listed oncogenicity label: Unknown Oncogenic Effect.
Somatic
This variant does not lie in a statistically significant hotspot. This variant has previously been reported in somatic cancers (COSMIC; COSV104587071, n = 2 times).
Cancer Hotspots
This variant does not lie in a statistically significant hotspot.